In an effort to identify genes involved in the early stages of tumor progression, Bryne JA et al (1995, Cancer Res 55:2896-2903) screened human breast and basal cell carcinomas for genes commonly overexpressed in tumor cells relative to non-tumor tissue. One novel sequence, D52, was differentially expressed in carcinoma cells and showed little homology to other genes. Chen SL et al (1996, Oncogene 12:741-751) independently cloned D52 based on its increased expression in lung tumor derived cell lines relative to cell lines derived from normal tissues. Recently, Byrne et al (1996, Genomics 35:523-532) described a human homolog of D52, termed D53, which is often coexpressed with D52 and may form hetero- or homo-dimers. Both D52 and D53 contain PEST domains, regions that are rich in amino acid residues proline (P), glutamate (E), serine (S), and threonine (T) (Rechsteiner M (1990) Semin Cell Biol 1:433-440). In human D52, 18 of 37 amino terminal residues are PEST domain residues (Byrne et al, supra). PEST domains are associated with rapidly degraded enzymes, transcriptional factors, and components of receptor signaling pathways (Loetscher P et al (1991) J Biol Chem 266:11213-11220). Caenorhabditis elegans open reading frame (ORF) F13E6.1 has homology to D52 (Wilson R et al (1994) Nature 368:32-38).
Tumor Proteins and Disease
Cancer remains a major public health concern, and current preventative measures and treatments do not match the needs of most patients. For example, among women in the United States, as many as one in eight will contract breast cancer in their lifetime (Helzlsouer KJ (1994) Curr Opin Oncol 6:541-548). Furthermore, the incidence of breast cancer is rising by about 1% a year (Harris JR et al (1992) N Engl J Med 327:319-328). Among men over 50 years of age, the lifetime risk of prostate cancer is 9.5% and of death from prostate cancer is 2.9% (McLellan DL et al (1995) Can Med Assoc J 153:895-900).
Genes may be differentially expressed in tumor cells relative to non-tumor cells. For example, elevated expression levels of 12-lipooxygenase correlate with advanced stage and poor differentiation of human prostate cancer (Gao X et al (1995) Urology 46:227-237). Additionally, the high incidence of HER2 gene overexpression in breast tumors suggests that perturbations in HER2 are among the earliest and most common genetic lesions in human breast cancer (Liu E et al (1992) Oncogene 7:1027-1032). This correlation has led to the development of potential HER2 specific therapeutics (Kern JA et al (1993) Am J Respir Cell Mol Biol).
The discovery of additional tumor associated genes may provide agents which are more efficacious in cancer diagnosis and treatment than HER2 and 12-lipooxygenase. Novel tumor associated genes may be specific to a different spectrum of tumor types than known genes. A new tumor protein would satisfy a significant need in the art by providing new agents for the diagnosis, prevention, and treatment of cancer.